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Chemical Structure| 1338466-77-5 Chemical Structure| 1338466-77-5

Structure of EPZ004777
CAS No.: 1338466-77-5

Chemical Structure| 1338466-77-5

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EPZ004777 is a potent, selective DOT1L inhibitor with IC50 of 0.4 nM in a cell-free assay and demonstrates > 1,200-fold selectivity for DOT1L over all other tested PMTs.

4.5 *For Research Use Only !

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Product Citations

Product Citations

Liu, Zhiwei ; Liu, Yingluo ; Qian, Lili ; Jiang, Shangwen ; Gai, Xiameng ; Ye, Shu , et al.

Abstract: KRAS mutant cancer, characterized by the activation of a plethora of phosphorylation signaling pathways, remains a major challenge for cancer therapy. Despite recent advancements, a comprehensive profile of the proteome and phosphoproteome is lacking. This study provides a proteomic and phosphoproteomic landscape of 43 KRAS mutant cancer cell lines across different tissue origins. By integrating transcriptomics, proteomics, and phosphoproteomics, we identify three subsets with distinct biological, clinical, and therapeutic characteristics. The integrative analysis of phosphoproteome and drug sensitivity information facilitates the identification of a set of drug combinations with therapeutic potentials. Among them, we demonstrate that the combination of DOT1L and SHP2 inhibitors is an effective treatment specific for subset 2 of KRAS mutant cancers, corresponding to a set of TCGA clinical tumors with the poorest prognosis. Together, this study provides a resource to better understand KRAS mutant cancer heterogeneity and identify new therapeutic possibilities.

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Product Details of EPZ004777

CAS No. :1338466-77-5
Formula : C28H41N7O4
M.W : 539.67
SMILES Code : O=C(NC1=CC=C(C(C)(C)C)C=C1)NCCCN(C[C@H]2O[C@@H](N3C=CC4=C(N)N=CN=C43)[C@H](O)[C@@H]2O)C(C)C
MDL No. :MFCD25563264
InChI Key :WXRGFPHDRFQODR-ICLZECGLSA-N
Pubchem ID :56962336

Safety of EPZ004777

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of EPZ004777

epigenetics

Isoform Comparison

Biological Activity

Target
  • Histone Methyltransferase

    DOT1L, IC50:0.4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MLL-AF10 and CALM-AF10 transformed LSK cells 10 µM 2 weeks To test the effect of EPZ004777 on the colony forming ability, results showed significantly fewer compact colonies were formed. Leukemia. 2013 Apr;27(4):813-22.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice MLL-AF10 and CALM-AF10 transformed cells Injection 10 µM 2 weeks To assess the spleen-colony forming ability post-treatment, results showed that treated cells failed to form any large spleen colonies. Leukemia. 2013 Apr;27(4):813-22.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.19mL

9.26mL

1.85mL

0.93mL

18.53mL

3.71mL

1.85mL

References

 

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